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Session IV: New Approaches to Improved Radiopharmaceuticals and Targeting

Retargeting Interleukin 13 for Radioimmunodetection and Radioimmunotherapy of Human High-grade Gliomas

Waldemar Debinski and Jeffrey P. Thompson
Waldemar Debinski
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Jeffrey P. Thompson
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DOI:  Published October 1999
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Abstract

A vast majority of patients with glioblastoma multiforme (GBM), a high-grade glioma, overexpress abundant amounts of a receptor for interleukin (IL)-13 in situ. This receptor is more restrictive because it is IL-4-independent and therefore differs from the IL-13/4 signaling receptor of normal tissue that is shared with IL-4. We previously identified one of the sites on the human IL (hIL)-13 molecule that is important for its interaction with the IL-13/4 receptor, a residue of glutamic acid at position 13. In this study, we mutated the cytokine and produced hIL-13.E13Y, in which the glutamic acid was substituted by tyrosine. This additional tyrosine residue was therefore strategically located within the region of IL-13 interaction with the signaling physiological receptor. hIL-13.E13Y did not transduce signals through the IL-13/4 receptor, whereas its interaction with the more restrictive, GBM-associated receptor remained intact. The mutated hIL-13 could be readily radiolabeled. Radiolabeled hIL-13.E13Y produced specific autoradiographic images of human GBM specimens. We demonstrate an effective way to redirect hIL-13 to its more restrictive receptor found in high-grade gliomas by mutagenizing the cytokine, and, concomitantly, we equipped hIL-13 with an additional tyrosine residue for higher specific activity radiolabeling.

Footnotes

  • ↵1 Presented at the “Seventh Conference on Radioimmunodetection and Radioimmunotherapy of Cancer,” October 15–17, 1998, Princeton, NJ. Supported by the Four Diamonds Fund Grant, Surgery Feasibility Grant, and NIH Grant R01 CA74145.

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October 1999
Volume 5, Issue 10
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Retargeting Interleukin 13 for Radioimmunodetection and Radioimmunotherapy of Human High-grade Gliomas
Waldemar Debinski and Jeffrey P. Thompson
Clin Cancer Res October 1 1999 (5) (10) 3143s-3147s;

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Retargeting Interleukin 13 for Radioimmunodetection and Radioimmunotherapy of Human High-grade Gliomas
Waldemar Debinski and Jeffrey P. Thompson
Clin Cancer Res October 1 1999 (5) (10) 3143s-3147s;
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Clinical Cancer Research
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